Efficacy and safety of linaclotide for opioid-induced constipation in patients with chronic noncancer pain syndromes from a phase 2 randomized study. Issue 5 (May 2020)

• Record Type: Journal Article
• Authors: Brenner, Darren M.; Argoff, Charles E.; Fox, Susan M.; Bochenek, Wieslaw; D'Astoli, Patricia; Blakesley, Rick E.; Reasner, David S.; O'Dea, Christopher R.; Cash, Brooks D.
• Is Part Of: Pain. Volume 161:Issue 5(2020)
• Publication Date: 2020-05
• Subjects: Bowel movement -- Guanylate cyclase-C agonist -- Opioid use -- Opioid constipation; Pain -- Periodicals; Douleur -- Périodiques; Anesthésie -- Périodiques; Pain; Electronic journals; Periodicals; Electronic journals; 616.0472
• DOI: 10.1097/j.pain.0000000000001754
• Languages: English
• ISSNs: 0304-3959

Abstract

Abstract : Abstract: Constipation is the most common adverse event (AE) of opioid therapy. This multicenter, phase 2 study evaluated the efficacy and safety of linaclotide in treating opioid-induced constipation (OIC) in patients with chronic noncancer pain syndromes (NCT02270983). Adults with OIC (<3 spontaneous bowel movements [SBMs]/week) related to chronic noncancer pain were randomized 1:1:1 to receive linaclotide 145 µg, linaclotide 290 µg, or placebo once daily for 8 weeks. The primary endpoint was change from baseline in 8-week SBM frequency rate (SBMs/week). Secondary efficacy endpoints included 6/8-week SBM 3 + 1 responders, time to first SBM, and changes from baseline in 8-week stool consistency, abdominal bloating, and straining. Additional endpoints included treatment satisfaction and adequate relief responders. In total, 254 patients were randomized: 87, 88, and 79 received linaclotide 145 µg, linaclotide 290 µg, and placebo, respectively. The mean changes from baseline in SBMs/week during the treatment period were 2.9 and 3.5 in the linaclotide 145 and 290 µg groups ( P < 0.01 for both doses), respectively, vs 1.6 in the placebo group. Diarrhea, the most common AE, was generally mild, resulting in 1.1%, 5.7%, and 1.3% of patients discontinuing in the linaclotide 145 μg, linaclotide 290 μg, and placebo groups, respectively. No serious AEs related to diarrhea were reported in any treatment group. Compared with placebo, linaclotide-treated patients had significant improvements in stool consistency, straining, abdominal bloating, and treatment satisfaction scores ( P < 0.05). Linaclotide significantly improved OIC symptoms and was well tolerated in patients with chronic noncancer pain. Abstract : Supplemental Digital Content is Available in the Text.In patients with chronic noncancer pain and opioid-induced constipation, linaclotide significantly improved stool consistency, straining, abdominal bloating, and treatment satisfaction vs placebo and was well tolerated.